P50 Percent Habituation Score [ Time Frame: baseline and after three days of intervention ] [ Designated as safety issue: No ]

This is an electrophysiological measure of arousal - a percent change in the P50 evoked response potential amplitudes with a 250 ms inter stimulus interval. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).

Secondary Outcome Measures:

PVT Fastest 10 Percent of Reaction Times [ Time Frame: baseline and after three days of intervention ] [ Designated as safety issue: No ]

This is a behavioral measure of arousal - the fastest 10 percent of all cued reaction time trials. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).

Power Function Exponent for Oral Bolus Estimation [ Time Frame: baseline and after three days of intervention ] [ Designated as safety issue: No ]

This is a behavioral measure of sensation in the oral cavity. The power function exponent is equal to the slope of a regression equation relating bolus size to a person's estimate of that size. An exponent below one implies an underestimate of bolus size. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).

Time to Swallow Puree Food [ Time Frame: baseline and after three days of intervention ] [ Designated as safety issue: No ]

This is a behavioral measure of swallowing - the time it takes for pureed food to transition across a part of the throat. The difference score is calculated as CPS - placebo and as modafinil - placebo (for stroke subjects only).

Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.

Behavioral: Baseline

Observations made at baseline before any intervention

Other Name: baseline observation

Behavioral: CPS

Submerging each participant's foot into ice water (36-44 F) for 50 seconds.

Other Name: cold pressor stimulation

Behavioral: Post CPS

20 minutes following the CPS condition.

Other Name: post cold pressor stimulation

Behavioral: Follow up

Follow up testing occurred at 3 months

Other Name: three month follow up

Active Comparator: stroke subjects

Stroke subjects are persons who have had a stroke affecting the right hemisphere and are subject to neglect or dysphagia who receive modafinil, placebo, baseline, CPS, Post CPS and Follow up interventions.

Drug: Modafinil

200 mg once daily with morning meal for three days administered only to stroke patients

Other Name: Provigil

Drug: Placebo

Subjects will receive a placebo designed to look like 200 mg dose of modafinil. The dose will be taken once daily with the morning meal for three days and will only be administered to stroke patients

Other Name: inert

Behavioral: Baseline

Observations made at baseline before any intervention

Other Name: baseline observation

Behavioral: CPS

Submerging each participant's foot into ice water (36-44 F) for 50 seconds.

Other Name: cold pressor stimulation

Behavioral: Post CPS

20 minutes following the CPS condition.

Other Name: post cold pressor stimulation

Behavioral: Follow up

Follow up testing occurred at 3 months

Other Name: three month follow up

Detailed Description:

Neglect and dysphagia are two of the most problematic behavioral disorders encountered in stroke rehabilitation with 300,000 patients affected annually in the US. Both disorders impede progress in therapy and both lead to costly medical complications, like falls which are associated with neglect and aspiration pneumonia and malnutrition which are associated with dysphagia. No widely accepted pharmacological treatment exists for either disorder.

A new direction of this application is to view neglect and dysphagia as different disorders that share a common deficit in magnitude estimation (ME). ME refers to one's ability to perceive the intensity of sensory stimulation. Deficits in ME explain how much of a stimulus is neglected by stroke patients. Sensory deficits are also known to produce dysphagia. Perceptual deficits influence how patients response to stimuli like failing to act on all stimuli present (neglect) and failing to generate swallowing reflexes sufficient for normal bolus flow (dysphagia).

We know from previous work that ME is altered by change in cortical arousal following stroke (decreased or hypoarousal). Hypoarousal is evidenced by objective and subjective post-stroke fatigue and daytime sleepiness which occurs in 50% of stroke patients and can persist chronically. Increasing arousal could potentially reverse the perceptual deficits associated with hypoarousal and improve neglect and dysphagia. This proposal manipulates arousal in two ways. Cold pressor stimulation (CPS), immersing the foot in cold water for 50 seconds, is used to increase arousal and reverse neglect and dysphagia temporarily. A brief, 3-day trial of modafinil (Provigil) versus placebo is then used in stroke patients to learn if a positive response to cold-pressor stimulation can predicts patients who respond positively to modafinil.

Concomitant medications excluded: Based on recommendations of manufacturer, the following concomitant medications are excluded: Tricyclic antidepressants and Monoamine oxidase (MAO) inhibitors. Any other CNS stimulation producing medications. Antifungal agents Itraconazole or Ketoconazole as plasma concentrations of modafinil may be increased.

Stroke patients will be excluded from the modafinil trial if they cannot swallow a capsule.

Stroke patients are excluded if they are able to become pregnant

Any other criteria that the PI or study physicians feel would put the volunteer's health at risk during the course of the study

Contacts and Locations

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For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01085903

Locations

United States, Arkansas

Conway Regional Rehabilitation Hospital

Conway, Arkansas, United States, 72035

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

Sponsors and Collaborators

University of Arkansas

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)